Abstract：
The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.
摘要：
生长激素促分泌素受体（GHS-R）和生长激素释放激素受体（GHRH-R）的负协调参与了细胞损伤的修复过程。在CPA治疗诱导的正常昆明小鼠和仓鼠不育模型中，比较了变构U-或H-样修饰的GHRH二聚体Grinodin和2Y。每个仓鼠干细胞衰竭模型皮下给药1-3-9µgGrinodin或2Y，每周一次，分别诱导75-69-46或45-13-50%的出生率。相比之下,类似的人更年期促性腺激素(hMG)或人生长激素(hGH)葡萄胎每天给药一次,但只引起25%或20%的出生率.Grinodin比2Y诱导更多的大卵泡和黄体，HMG,HGH.hMG治疗组观察到许多扭曲的间质细胞和更多的结缔组织，而hGH治疗组的卵泡很少。2Y在小鼠中具有21天的血浆寿命和更高的GH释放，诱导较低的出生率和更强的生殖个体特异性，以及仅促进模型中的间充质干细胞（MSC）的增殖。相比之下,Grinodin的血浆寿命为30天，小鼠的GH释放低得多。通过增加Ki67和GHS-R的表达显著促进卵巢MSCs的增殖和活化以及卵泡的发育。并以剂量依赖性方式降低GHRH-R的表达。然而,模型中的高GH和过量雌激素水平显示出生育率的剂量依赖性降低.因此,与2Y不同，低剂量的Grinodin特别表现出低GHS-R和高GHRH-R表达，从而逃避GH和雌激素的释放，改善器官功能，导致生育率的增加。
